The initiation of an adaptive immune response involves the presentation of antigen to T lymphocytes. Which cells are capable of carrying out this process is still not completely decided. Consensus exists for the role of interdigitating dendritic cells, but the role of the B lymphocyte is more controversial. During the past year we addressed this issue by using T cell receptor transgenic mice as a source of antigen-specific, naive CD4+ T cells and testing the ability of these cells to be stimulated to produce interleukin-2 (IL-2) by resting and activated B cells. Activated B cells were capable of stimulating such T cells but resting B cells were not. When compared to dendritic cells, however, activated B cells were less efficient, requiring more cells per culture well and stimulating less IL-2 per T cell. This deficiency appeared to be caused by an inadequate amount of costimulatory activity, because it could be corrected by the addition of an anti-CD28 antibody but not by increasing the concentration of antigen. Resting B cells also functioned in the presence of anti-CD28 antibody suggesting that the ability to deliver costimulation is the major limitation that needs to be overcome in B cell activation of naive CD4+ T cells.